Restricted Access Volatile Supramolecular Solvents for Single-Step Extraction/Cleanup of Benzimidazole Anthelmintic Drugs in Milk Prior to LC-MS/MS

In this work, a restricted access volatile supramolecular solvent (RAM-VOL-SUPRAS) directly synthesized in milk is proposed for the first time for the simultaneous extraction and cleanup of benzimidazole anthelmintic drugs in milk meant for human consumption. The RAM-VOL-SUPRAS was formed by the self-assembly and coacervation of hexanol in tetrahydrofuran induced by the water content in milk. Benzimidazoles legislated by the European Union were quantitatively extracted (80–110%), and proteins were precipitated by the action of THF and the amphiphile; extraction of carbohydrates was avoided by a size exclusion mechanism, and lipids were removed during hexanol evaporation. The analytical methodology was fully validated according to Commission Decision 2002/657/EC. Method detection limits from 0.03 to 0.14 μg L–1 were well below the maximum residue limits legislated in milk for these drugs, with interday precisions at maximum residue levels below 13%. This novel methodology guarantees a rapid and reliable to...